Ca2+ entry blockers, force staircase and the onset of the positive inotropic action of cardiotonic steroids in isolated cardiac muscle.
1. Effects of alterations of Ca2+ fluxes on the force staircase phenomenon and on the positive inotropic action of strophanthidin or ouabain were examined in left atrial muscle preparations isolated from rabbit or rat heart. 2. The organic Ca2+ entry blockers converted the positive force staircase observed in rabbit heart to the negative staircase; however, Ni2+, Co2+ or a reduction of the extracellular Ca2+ concentration which reduces Ca2+ influx via the Na+/Ca2+ exchange mechanism as well as via the Ca2+ channels, failed to convert the force staircase. 3. All of these interventions or ryanodine, which inhibits Ca2+ release from the sarcoplasmic reticulum, delayed the onset of the positive inotropic effect of strophanthidin or ouabain without reducing the peak inotropic effect. 4. These results indicate that either Ca2+ antagonists reduce the Na+ influx in addition to reducing Ca2+ influx, or Ca2+ influx per se and not the Na+ influx is important for the staircase phenomenon, and that intracellular Ca2+ accumulation plays an important role in the early phase of the positive inotropic effect of the cardiotonic steroids.
Kyosuke
T
T
Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Aomori, Japan.
Kondo
H
H
Hirano
H
H
Kitazawa
T
T
Akera
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002301:Cardiac Glycosides / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013327:Strophanthidin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002301:Cardiac Glycosides; D012433:Ryanodine; D010042:Ouabain; D013327:Strophanthidin; D002118:Calcium